Results from a global phase 3 clinical trial found that maintenance therapy with a combination of lurbinectedin and atezolizumab helped some patients with extensive-stage small cell lung cancer (ES-SCLC) live longer compared to maintenance therapy with atezolizumab alone.

The research will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 30-June 3 in Chicago. 

“While the introduction of immunotherapy in first-line treatment has improved outcomes, advanced small cell lung cancer remains difficult to treat. The phase 3 IMforte trial shows that the new treatment combination of lurbinectedin and atezolizumab given as maintenance therapy after first-line treatment helps people live longer and reduces the risk of disease progression or death. This outcome represents a major milestone and could provide a much-needed option for advancing the treatment of this aggressive disease,” said lead study author Luis G. Paz Ares, MD, PhD, 12 de Octubre University Hospital in Madrid, Spain.

The IMforte trial included 660 patients with previously untreated ES-SCLC, no history of metastases to the brain or spinal cord, and good performance status. All patients enroled in the study received standard-of-care induction therapy of atezolizumab, carboplatin, and etoposide in 4 cycles. 

After induction therapy, patients were eligible to continue in the study if they had an ongoing tumour response or stable disease after 4 cycles. There were 483 patients who went on to receive maintenance therapy.

They were randomly assigned to receive either lurbinectedin and atezolizumab (242 patients) or atezolizumab alone (241 patients).

The participants were from 91 study sites in 13 different countries. Approximately 82% were White, 13% were Asian, and 5% had another racial origin. Around 7% were Hispanic or Latino.

The median age of the participants was 66 years, and approximately 63% of the patients were men.

Key Findings

• After a median follow-up of 15 months, the median progression-free survival (PFS) was 5.4 months in the lurbinectedin and atezolizumab arm versus 2.1 months in the atezolizumab alone arm.
• Patients treated with lurbinectedin and atezolizumab had a 46% lower risk of cancer progression than those treated with atezolizumab alone.
• The median overall survival was 13.2 months for patients treated with lurbinectedin and atezolizumab and 10.6 months for patients treated with atezolizumab alone.
• Patients treated with lurbinectedin and atezolizumab had a 27% lower risk of death than those treated with atezolizumab alone.
• The median treatment duration was 4.1 months on lurbinectedin and 4.2 months on atezolizumab in the lurbinectedin and atezolizumab arm. In the atezolizumab alone arm, it was 2.1 months. A longer treatment duration can often provide greater benefit as more doses of the drug are tolerated.

There was a noted difference in adverse events between the two groups.

Treatment-related adverse events occurred in 83.5% of patients in the lurbinectedin and atezolizumab arm, compared to 40% in the atezolizumab alone arm.

In the lurbinectedin and atezolizumab arm, 25.6% of patients experienced a grade 3 or 4 adverse event and 0.8% experienced a grade 5 adverse event. In the atezolizumab alone arm, 5.8% experienced a grade 3 or 4 adverse event and 0.4% experienced a grade 5 adverse event.

In the lurbinectedin and atezolizumab arm, 6.2% of patients stopped treatment due to side effects compared to 3.3% in the atezolizumab alone arm. 

“Immunotherapy has improved survival outcomes for patients with extensive-stage small cell lung cancer (ES-SCLC), marking meaningful progress in a historically challenging disease. However, despite these advances, long-term outcomes remain suboptimal, underscoring the need for better strategies. The integration of lurbinectedin—a novel DNA-damaging agent—into the maintenance setting alongside atezolizumab following initial chemo-immunotherapy represents an important next step. This approach offers a way to extend disease control and may signal a shift toward more durable benefit for patients,” said Charu Aggarwal, MD, MPH, FASCO, Leslye M Heisler Professor of Lung Cancer Excellence at University of Pennsylvania – Abramson Cancer Center, and an ASCO Expert in lung cancer.

Next Steps

The IMforte study is ongoing. Researchers will continue to follow enroled patients.

They are also considering other settings in which to use this treatment combination, such as first-line therapy. 

Source: ASCO